The National Cancer Institute (NCI) is continuing to pursue clinical trials concepts that incorporate genomics into the evolving national strategy for precision medicine. Recent advances in knowledge of the molecular abnormalities in tumors that either drive proliferation or promote survival have led to the development of many therapeutic agents that target those abnormalities. Studies will screen for molecular features that may predict response to a targeted agent with a specific mechanism of action. In some cases, the study designs will use an umbrella protocol whereby a single entry point for molecular screening will then distribute patients to multiple, single-arm phase 2/3 trials. One example of the trials in the series, MATCH, was open for patient enrollment in July 2015. Other trials will use enrichment designs where the particular molecular characteristic is an eligibility criterion and the therapy is limited to such patients.